Drug discovery is a sophisticated process that incorporates scientific innovations and cuttingedge technologies.Compared to traditional bioactivity-based screening methods,encoding and display technologies for combina...Drug discovery is a sophisticated process that incorporates scientific innovations and cuttingedge technologies.Compared to traditional bioactivity-based screening methods,encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency,throughput,and resource minimization.This review systematically summarizes the development history,typology,and prospective applications of encoding and displayed technologies,including phage display,ribosomal display,mRNA display,yeast cell display,one-bead one-compound,DNA-encoded,peptide nucleic acidencoded,and new peptide-encoded technologies,and examples of preclinical and clinical translation.We discuss the progress of novel targeted therapeutic agents,covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear,monocyclic,and bicyclic peptides,in addition to antibodies.We also address the pending challenges and future prospects of drug discovery,including the size of screening libraries,advantages and disadvantages of the technology,clinical translational potential,and market space.This review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.展开更多
基金supported by the National Natural Science Foundation of China(82304698 and 32300317)Science and Technology Development Fund,Macao SAR(file nos.0048/2023/ITP2,0150/2022/A3,001/2023/ALC,0006/2020/AKP and 005/2023/SKL,China)+3 种基金Guangdong Basic and Applied Basic Research Foundation(grant nos 2021A1515110338,China)Natural Science Foundation of Guangdong Province(2024A1515012659 and 2023B1515120023,China)Shenzhen-Hong Kong-Macao S&T Program(Category C)(SGDX2020110309420200,China)the Research Fund of University of Macao(CPG2024-00038-ICMS,China).
文摘Drug discovery is a sophisticated process that incorporates scientific innovations and cuttingedge technologies.Compared to traditional bioactivity-based screening methods,encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency,throughput,and resource minimization.This review systematically summarizes the development history,typology,and prospective applications of encoding and displayed technologies,including phage display,ribosomal display,mRNA display,yeast cell display,one-bead one-compound,DNA-encoded,peptide nucleic acidencoded,and new peptide-encoded technologies,and examples of preclinical and clinical translation.We discuss the progress of novel targeted therapeutic agents,covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear,monocyclic,and bicyclic peptides,in addition to antibodies.We also address the pending challenges and future prospects of drug discovery,including the size of screening libraries,advantages and disadvantages of the technology,clinical translational potential,and market space.This review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.
